NCT04697628 - Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer | Crick

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria * Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and: * Has experienced disease progression during or after treatment with a standard of care systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as either: * paclitaxel + cisplatin + bevacizumab + anti-PD-(L)1 agent, or * paclitaxel + carboplatin + bevacizumab + anti-PD-(L)1 agent, or * paclitaxel + topotecan/nogitecan + bevacizumab + anti-PD-(L)1 agent * Note: In cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of care therapy or the participant was ineligible for such treatment according to local standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required. * Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy, should not be counted as a systemic therapy regimen. Single agent therapy with an anti-PD(L)1 agent for r/mCC cancer should be counted. * Measurable disease according to RECIST v1.1 as assessed by the investigator. * Has ECOG performance status of 0 or 1 prior to randomization. * Has life expectancy of at least 3 months. Exclusion Criteria * Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned as part of the inclusion criteria above. * Has clinically significant bleeding issues or risks. This includes known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry. * Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack \>1 month prior to screening is allowed). * Active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory conditions that predispose to cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), ocular Stevens-Johnson syndrome or toxic epidermal necrolysis, mucus pemphigoid, and participants with penetrating ocular transplants. Cataracts alone is not an exclusion criterion. * Major surgery within 4 weeks or minor surgery within 7 days prior to the first study treatment administration. * Peripheral neuropathy ≥grade 2. * Any prior treatment with monomethyl auristatin E (MMAE)-containing drugs. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Outcomes

Primary Outcomes

Overall Survival

Overall survival is defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.

Time frame: From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum up to 25 months)

Secondary Outcomes

Progression Free Survival (PFS) as Assessed by Investigator

PFS per investigator was defined as the time from the date of randomization to the first documentation of disease progression (PD) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, or death due to any cause, whichever occurred earlier. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Participants without evidence of radiographic disease progression or death were censored at the date of last adequate tumor assessment prior to data cut-off date or start of new anti-cancer therapy. Participants with disease progression or death that occurred after 2 or more missed scans were censored at the last adequate tumor assessment prior to missed scans. Participants without post-baseline scan data were censored at the day of randomization.

Time frame: From the date of randomization to first documentation of PD or death due to any cause, or censoring date whichever occurred first (maximum up to 25 months)

Confirmed Objective Response Rate (ORR) as Assessed by Investigator

Confirmed objective response rate was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The minimum criteria for stable disease (SD) duration are defined as ≥ 5 weeks after the date of randomization. For a response to be considered as confirmed, the subsequent response had to be at least 4 weeks after the initial response. Two-sided 95% exact confidence interval (CI) was computed using the Clopper-Pearson method.

Time frame: From the date of randomization until date of confirmed CR or PR (maximum up to 25 months)

Time-to-Response (TTR) as Assessed by the Investigator

TTR was defined as the time from the randomization date to the date of the first confirmed objective response (CR or PR that was subsequently confirmed). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From the date of randomization to date of date of the first confirmed objective response (maximum up to 25 months)

Duration of Response (DOR) by Investigator Assessment

DOR was defined as the time from the date of the first confirmed objective response (CR or PR that was subsequently confirmed) to the date of the first documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Time frame: From the date of first documented response of CR or PR to the first documented PD or death from any cause, whichever occurred first (maximum up to 25 months)

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment and with onset date on or before 30 days after the last dose of study treatment.

Time frame: From start of treatment up to 30 days after last dose of study treatment (up to 25 months)

EuroQOL Five Dimensions Five Level (EQ-5D-5L) Index Score

The EQ-5D-5L questionnaire is a 5-item self-reported measure of functioning and well-being, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems and extreme problems). Responses to the 5 items are then converted to a weighted health state index (utility score) based on values derived from general population samples. This health utility score is between 0 and 1, where 0 is death and 1 is perfect health.

Time frame: From start of treatment until end of follow-up

EQ-5D Visual Analog Scale (VAS) Scores

EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state) ; higher scores indicate a better health state.

Time frame: From start of treatment until end of follow-up

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Total Score

The EORTC-QLQ-C30 questionnaire is composed of 30 questions for which the answers ranges either from 1 (not at all) to 4 (very much) for items 1 to 28, or from 1 (very poor) to 7 (excellent) for items 29 to 30. The EORTC QLQ-C30 scale scores will be calculated using the EORTC QLQ-C30 Scoring Manual. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items (i.e., no item occurs in more than one scale). All of the scales and single-item measures range in score from 0 to 100, with a high scale score representing a higher response level (e.g., a high level of functioning, a high QoL, or a high level of symptomatology/problems)

Time frame: From start of treatment until end of follow-up

EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores

The EORTC QLQ-CX24 questionnaire is meant for use among cervical cancer participants varying in disease stage and treatment modality. The EORTC-QLQ-CX24 questionnaire is composed of 24 questions for which the answers ranged from 1 (Not at all) to 4 (Very much). Four functional scales and 5 symptom scales will be calculated using the EORTC QLQ-CX24 Scoring Manual. The 9 scores computed from the EORTC-QLQ-CX24 questionnaire will be summarized by treatment arm using descriptive statistics.

Time frame: From start of treatment until end of follow-up

Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer

Overview

Conditions

Interventions

Eligibility

Locations (211)

Outcomes

Primary Outcomes

Secondary Outcomes